2,3-bis(benzyloxy)-2,5-difluorophenatholamine | 152434-83-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,3-bis(benzyloxy)-2,5-difluorophenatholamine
• 英文别名: Benzeneethanamine, 3,4-dibenzyloxy-2,5-difluoro-；2-amino-1-[2,5-difluoro-3,4-bis(phenylmethoxy)phenyl]ethanol
• CAS: 152434-83-8
• 化学式: C₂₂H₂₁F₂NO₃
• 分子量: 385.41
• InChiKey: ZDEXCLYGTAFNLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3-bis(benzyloxy)-2,5-difluorophenatholamine 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 15.0h， 生成 2,5-difluoroepinephrine oxalate
  参考文献：
  名称：

  Syntheses of 2,5- and 2,6-difluoronorepinephrine, 2,5-difluoroepinephrine, and 2,6-difluorophenylephrine: effect of disubstitution with fluorine on adrenergic activity

  摘要：

  Synthetic routes to difluorinated analogs of the adrenergic agonists, norepinephrine (NE), epinephrine (E), and phenylephrine (PE) have been developed. The syntheses were based on elaboration of the ethanolamine side chains from the appropriately polyfunctionalized benzaldehydes, The benzaldehydes were prepared from precursor difluorinated benzenes by sequential regioselective lithiations and reaction with electrophiles to introduce hydroxyl and carboxaldehyde functionalities. Binding and functional assay data demonstrate that the 2,6-difluorinated analogs are relatively inactive at both alpha- and beta-adrenergic receptors. These results are consistent with earlier observations that 2-fluoro substitution of adrenergic agonists decreases alpha-adrenergic activity whereas 6-fluoro substitution decreases beta-adrenergic activity.

  DOI：

  10.1021/jm00076a024
• 作为产物：
  描述：

  2,5-二氟苯酚 在 lithium aluminium tetrahydride 、 正丁基锂 、 硼酸三甲酯 、 双氧水 、 potassium carbonate 、 zinc(II) iodide 作用下， 以 乙醚 、 氯仿 、 丙酮 为溶剂， 反应 5.25h， 生成 2,3-bis(benzyloxy)-2,5-difluorophenatholamine
  参考文献：
  名称：

  Syntheses of 2,5- and 2,6-difluoronorepinephrine, 2,5-difluoroepinephrine, and 2,6-difluorophenylephrine: effect of disubstitution with fluorine on adrenergic activity

  摘要：

  Synthetic routes to difluorinated analogs of the adrenergic agonists, norepinephrine (NE), epinephrine (E), and phenylephrine (PE) have been developed. The syntheses were based on elaboration of the ethanolamine side chains from the appropriately polyfunctionalized benzaldehydes, The benzaldehydes were prepared from precursor difluorinated benzenes by sequential regioselective lithiations and reaction with electrophiles to introduce hydroxyl and carboxaldehyde functionalities. Binding and functional assay data demonstrate that the 2,6-difluorinated analogs are relatively inactive at both alpha- and beta-adrenergic receptors. These results are consistent with earlier observations that 2-fluoro substitution of adrenergic agonists decreases alpha-adrenergic activity whereas 6-fluoro substitution decreases beta-adrenergic activity.

  DOI：

  10.1021/jm00076a024

文献信息

• Syntheses of 2,5- and 2,6-difluoronorepinephrine, 2,5-difluoroepinephrine, and 2,6-difluorophenylephrine: effect of disubstitution with fluorine on adrenergic activity
  作者：George T. Chen、Michael King、Fabian Gusovsky、Cyrus R. Creveling、John W. Daly、Bang Hua Chen、Jun Ying Nie、Kenneth L. Kirk

  DOI：10.1021/jm00076a024

  日期：1993.11

  Synthetic routes to difluorinated analogs of the adrenergic agonists, norepinephrine (NE), epinephrine (E), and phenylephrine (PE) have been developed. The syntheses were based on elaboration of the ethanolamine side chains from the appropriately polyfunctionalized benzaldehydes, The benzaldehydes were prepared from precursor difluorinated benzenes by sequential regioselective lithiations and reaction with electrophiles to introduce hydroxyl and carboxaldehyde functionalities. Binding and functional assay data demonstrate that the 2,6-difluorinated analogs are relatively inactive at both alpha- and beta-adrenergic receptors. These results are consistent with earlier observations that 2-fluoro substitution of adrenergic agonists decreases alpha-adrenergic activity whereas 6-fluoro substitution decreases beta-adrenergic activity.